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Original Investigation
December 13, 2018

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood

Author Affiliations
  • 1Pediatric Oncology and Hematology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
  • 2Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham
  • 3Division of Hematology, Oncology and Bone Marrow Transplantation, University of Alabama at Birmingham
  • 4Danish Cancer Society Research Center, Copenhagen, Denmark
  • 5Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
  • 6Pediatric Hematology/Oncology, City of Hope, Duarte, California
  • 7Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis
  • 8Department of Pediatrics, School of Medicine, University of Alabama at Birmingham
JAMA Oncol. 2018;4(12):e182453. doi:10.1001/jamaoncol.2018.2453
Key Points

Question  What is the risk of late mortality after allogeneic blood or marrow transplantation performed in childhood, and has the rate of late mortality decreased over time?

Findings  In this cohort study of 1388 individuals who have lived 2 years or more after allogeneic blood or marrow transplantation performed in childhood, transplant recipients were at a continued elevated risk of premature death compared with the general population. Nonetheless, the rate of late mortality in this population has decreased during the past 3 decades.

Meaning  The risk of late mortality after allogeneic blood or marrow transplantation performed in childhood remains elevated for many years after transplantation, although the rate has decreased over time, and calls for lifelong proactive follow-up care.

Abstract

Importance  Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades.

Objectives  To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time.

Design, Setting, and Participants  A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016.

Exposure  Allogeneic BMT performed in childhood.

Main Outcomes and Measures  All-cause mortality, relapse-related mortality, and non–relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases.

Results  Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non–relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend).

Conclusions and Relevance  Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

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